The international study (NCT03321981) is assessing MCLA-128 in two types of metastatic breast cancer patients, including HER2-positive and hormone receptor positive/HER2-low patients.
MCLA-128 is a full-length bispecific antibody that targets HER2 and HER3 receptors. The antibody is the most-advanced of its kind, referred to as Biclonics.
MCLA-128 was engineered to overcome the resistance of cancer cells to HER2-targeted therapies by (1) blocking cellular growth and survival while simultaneously preventing tumor cells from escaping the therapy through activation of the HER3 molecular pathway, and (2) recruiting immune cells to kill the tumor. MCLA-128 was modified to enhance the immune cells’ ability to target the tumor.
Merus anticipates enrolling 120 patients in locations across Europe and the U.S. The first group will be composed of HER2-positive patients progressing on anti-HER2 therapies. Patients will receive MCLA-128 in combination with Herceptin (trastuzumab, by Genentech) and chemotherapy. In preclinical tests, MCLA-128 and Herceptin inhibited tumor cell growth regulated by HER3.
The second group will be comprised of metastatic breast cancer patients with hormone receptor positive status and HER2-low who are receiving hormone therapies and CDK4/6 inhibitors. Participants will receive MCLA-128 in combination with endocrine therapy, which showed effectiveness in preclinical studies.
The primary endpoint for the two groups is the clinical benefit rate — the proportion of patients who achieve at least disease stabilization — at 24 weeks of treatment. The study is recruiting patients (more information here).
“With promising single agent activity observed in heavily-pretreated patients underscoring the potential of MCLA-128 in [metastatic breast cancer], this study is designed to elucidate the activity of this important HER2/HER3-targeted candidate in combination with current standards of care in areas of unmet need,” Ton Logtenberg, PhD, Merus CEO, said in a press release.
MCLA-128 already had shown sustained treatment efficacy in a Phase 1/2 clinical trial (NCT02912949) in breast cancer patients who had failed other HER2 therapies. The study is ongoing and recruiting participants at several locations in Europe.
Merus also is evaluating MCLA-128 in gastric, ovarian, endometrial, and non-small cell lung cancers. The company said it expects to start defining a clinical plan for MCLA-128 in solid tumors beyond breast cancer in the second quarter of 2018.